Di Paola Davide, Capparucci Fabiano, Abbate Jessica Maria, Cordaro Marika, Crupi Rosalia, Siracusa Rosalba, D'Amico Ramona, Fusco Roberta, Genovese Tiziana, Impellizzeri Daniela, Cuzzocrea Salvatore, Spanò Nunziacarla, Gugliandolo Enrico, Peritore Alessio Filippo
Department of Chemical, Biological, Pharmaceutical, and Environmental Science, University of Messina, 98166 Messina, Italy.
Department of Veterinary Science, University of Messina, 98166 Messina, Italy.
Toxics. 2022 Feb 9;10(2):81. doi: 10.3390/toxics10020081.
Pharmaceuticals are actually identified as a threat to the ecosystem. Nowadays, the growing consumption of antineoplastic agents has been related to their continuous input in natural environments. These substances can interfere with physiological and biochemical processes of aquatic species over their entire life cycle. Oxaliplatin (OXA) is a widely used chemotherapeutic agent to treat colon or rectal cancer. This study was aimed to evaluate the developmental toxicity of the OXA exposure. To this end, zebrafish embryos were incubated with 0.001, 0.1, 0.5 mg/L OXA. At different timepoints mortality rate, hatching rate, developmental abnormalities, histological analysis, oxidative stress and mRNA expression of gene related to oxidative stress were evaluated. Our results showed that OXA exposure can induce increased mortality and developmental abnormalities reducing the hatching rate. Histological analysis demonstrated that OXA induced liver, intestine, muscle and heart injury. Superoxide dismutase and catalase activities were significantly increased after OXA exposure demonstrating its oxidative effects. The mRNA expression levels of apoptosis-related genes (caspase-3, bax and bcl-2) were significantly upregulated by OXA exposure. In conclusion, we highlighted that OXA exposure led to a dose-related developmental toxicity, oxidative stress and apoptosis.
药物实际上被视为对生态系统的一种威胁。如今，抗肿瘤药物消费量的不断增长与其在自然环境中的持续输入有关。这些物质会在整个生命周期中干扰水生物种的生理和生化过程。奥沙利铂（OXA）是一种广泛用于治疗结肠癌或直肠癌的化疗药物。本研究旨在评估奥沙利铂暴露的发育毒性。为此，将斑马鱼胚胎与0.001、0.1、0.5mg/L的奥沙利铂一起孵育。在不同时间点评估死亡率、孵化率、发育异常、组织学分析、氧化应激以及与氧化应激相关基因的mRNA表达。我们的结果表明，奥沙利铂暴露会导致死亡率增加和发育异常，降低孵化率。组织学分析表明，奥沙利铂会导致肝脏、肠道、肌肉和心脏损伤。奥沙利铂暴露后超氧化物歧化酶和过氧化氢酶活性显著增加，表明其具有氧化作用。奥沙利铂暴露显著上调了凋亡相关基因（caspase-3、bax和bcl-2）的mRNA表达水平。总之，我们强调奥沙利铂暴露会导致与剂量相关的发育毒性、氧化应激和凋亡。
